title: A non-comparative phase II study of dose intensive chemotherapy with doxorubicin and ifosfamide followed by high dose ICE consolidation with PBSCT in non-resectable, high grade, adult type soft tissue sarcomas.
abstract: The objective was to determine the role of dose intensive induction chemotherapy in patients with soft tissue sarcomas (STS) that were considered unresectable. Treatment consisted of 2-3 cycles of doxorubicin (Dox) and ifosfamide (Ifo) followed by high dose chemotherapy with ifosfamide, carboplatin, etoposide (HD-ICE) plus peripheral blood stem cell transplantation (PBSCT). 30 out of 631 consecutive patients, median age 46 years (21-62), with high grade STS were included. 29 patients completed at least 2 cycles of Dox/Ifo. HD-ICE was withheld because of progressive disease (PD) in 5 patients, neurotoxicity in 6 cases, insufficient peripheral blood stem cell (PBSC) mobilization, complete remission (CR) and refusal in 1 patient each. HD-ICE was associated with non-haematological grade III toxicity including emesis, mucositis, fever, neurotoxicity, and transaminase level elevation. Two additional patients attained a partial response after HD-ICE. Overall, 24 of 30 (80%) patients underwent surgery, with complete tumor resections in 19 patients (63% of all patients, 79% of the operated subgroup); however, 2 of these required amputation. After a median follow up period of 50 months in surviving patients (range, 26-120), 5-year PFS and OS rates were 39% and 48%, respectively. Induction chemotherapy plus consolidation HD-ICE is generally feasible, but is associated with significant neurotoxicity. The advantage of HD-ICE over conventional dose chemotherapy plus external beam radiation therapy (EBRT) in non-resectable disease remains unproven.
authors.affiliation: Medical Oncology, Comprehensive Cancer Center North, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Christian-Albrechts-University, Arnold-Heller-Str. 3, Haus 27, 24105, Kiel, Germany, joerg.hartmann@uksh.de.
authors.forename: Jörg Thomas
authors.initials: JT
authors.lastname: Hartmann
authors.forename: M
authors.initials: M
authors.lastname: Horger
authors.forename: T
authors.initials: T
authors.lastname: Kluba
authors.forename: A
authors.initials: A
authors.lastname: Königsrainer
authors.forename: P
authors.initials: P
authors.lastname: de Zwart
authors.forename: C Hann
authors.initials: CH
authors.lastname: von Weyhern
authors.forename: F
authors.initials: F
authors.lastname: Eckert
authors.forename: W
authors.initials: W
authors.lastname: Budach
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D055815:Young Adult
chemical_list: D005047:Etoposide; D004317:Doxorubicin; D016190:Carboplatin; D007069:Ifosfamide